title: Reduced-intensity conditioning by fludarabine/busulfan without additional irradiation or T-cell depletion leads to low non-relapse mortality in unrelated bone marrow transplantation.
abstract: In reduced intensity, allogeneic stem cell transplantation from unrelated donors (u-RIST), graft-versus-host disease (GVHD), graft failure, and non-relapse mortality (NRM) are persistent problems. Although anti-thymocyte globulin, alemtuzumab, and total body irradiation (TBI) have been explored as conditioning modalities for u-RIST, the necessity for T-cell depletion or TBI to prevent GVHD or facilitate engraftment in u-RIST has not been determined. We here report the use of u-RIST with bone marrow grafting, following a simple conditioning regimen of 180 mg/m(2) fludarabine and 8 mg/kg of oral or intravenous busulfan without TBI or T-cell depletion. The study population was exclusively Japanese patients with a history of prior chemotherapy. We retrospectively analyzed 31 consecutive patients (median age 53 years). Twenty-five patients (81%) were transplanted from HLA-A, -B, and -DRB1 allele-matched donors. In all patients, neutrophil engraftment was achieved. The cumulative incidence of grade II-IV acute GVHD was 42%. However, 77% of patients with acute GVHD improved with, and could be managed by, initial, systemic, high-dose steroid treatment alone. Two-year overall and event-free survival was 62 and 53%, respectively. The NRM of 10% at 2 years was relatively low. Our results suggest that u-RIST without TBI or T-cell depletion may improve the prognosis after u-RIST in certain patient populations.
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakane
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. hirohisa@msic.med.osaka-cu.ac.jp.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Koh
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Nakamae
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Nishimoto
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Inoue
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Aimoto
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Aimoto
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Terada
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Ki-Ryang
authors.initials: KR
authors.lastname: Koh
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000401:mortality; D002066:Busulfan / Q000627:therapeutic use*; D046528:Chimerism; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine